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DK0658159T3 - Arylidene and heteroarylidene oxindole derivatives as tyrosine kinase inhibitors - Google Patents

Arylidene and heteroarylidene oxindole derivatives as tyrosine kinase inhibitors

Info

Publication number
DK0658159T3
DK0658159T3 DK94918379T DK94918379T DK0658159T3 DK 0658159 T3 DK0658159 T3 DK 0658159T3 DK 94918379 T DK94918379 T DK 94918379T DK 94918379 T DK94918379 T DK 94918379T DK 0658159 T3 DK0658159 T3 DK 0658159T3
Authority
DK
Denmark
Prior art keywords
tyrosine kinase
kinase inhibitors
arylidene
oxindole derivatives
heteroarylidene
Prior art date
Application number
DK94918379T
Other languages
Danish (da)
Inventor
Franco Buzzetti
Antonio Longo
Maria Gabriella Brasca
Angelo Crugnola
Dario Ballinari
Mariangela Mariani
Fabrizio Orzi
Original Assignee
Pharmacia & Upjohn Spa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pharmacia & Upjohn Spa filed Critical Pharmacia & Upjohn Spa
Application granted granted Critical
Publication of DK0658159T3 publication Critical patent/DK0658159T3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/36—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/37—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by etherified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/41—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by carboxyl groups, other than cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids
    • C07C327/38—Amides of thiocarboxylic acids
    • C07C327/40—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C327/42—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of a saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/32—Oxygen atoms
    • C07D209/34—Oxygen atoms in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D215/14—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Indole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Quinoline Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

Oxindole, acrylamide, thioacrylamide and acrylonitrile compounds, and their pharmaceutically acceptable salts, which are useful as tyrosine kinase inhibitors.
DK94918379T 1993-07-01 1994-05-26 Arylidene and heteroarylidene oxindole derivatives as tyrosine kinase inhibitors DK0658159T3 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB939313638A GB9313638D0 (en) 1993-07-01 1993-07-01 Arylidene and heteroarylidene oxindole derivatives and process for their preparation
PCT/EP1994/001715 WO1995001349A1 (en) 1993-07-01 1994-05-26 Arylidene and heteroarylidene oxindole derivatives as tyrosine kinase inhibitors

Publications (1)

Publication Number Publication Date
DK0658159T3 true DK0658159T3 (en) 2000-12-18

Family

ID=10738142

Family Applications (1)

Application Number Title Priority Date Filing Date
DK94918379T DK0658159T3 (en) 1993-07-01 1994-05-26 Arylidene and heteroarylidene oxindole derivatives as tyrosine kinase inhibitors

Country Status (23)

Country Link
US (1) US5656654A (en)
EP (2) EP0987263B1 (en)
JP (1) JP3737826B2 (en)
KR (1) KR950702979A (en)
CN (1) CN1111454A (en)
AT (2) ATE360013T1 (en)
AU (1) AU679754B2 (en)
CA (1) CA2142472A1 (en)
DE (2) DE69425637T2 (en)
DK (1) DK0658159T3 (en)
ES (2) ES2152317T3 (en)
FI (1) FI950859A0 (en)
GB (1) GB9313638D0 (en)
GR (1) GR3034854T3 (en)
HU (1) HUT72047A (en)
IL (1) IL110131A0 (en)
MX (1) MX9404885A (en)
NZ (1) NZ267423A (en)
PL (1) PL307741A1 (en)
PT (1) PT658159E (en)
RU (1) RU95108244A (en)
WO (1) WO1995001349A1 (en)
ZA (1) ZA944730B (en)

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GB9501567D0 (en) * 1995-01-26 1995-03-15 Pharmacia Spa Hydrosoluble 3-arylidene-2-oxindole derivatives as tyrosine kinase inhibitors
US5880141A (en) * 1995-06-07 1999-03-09 Sugen, Inc. Benzylidene-Z-indoline compounds for the treatment of disease
US6906093B2 (en) 1995-06-07 2005-06-14 Sugen, Inc. Indolinone combinatorial libraries and related products and methods for the treatment of disease
US6147106A (en) 1997-08-20 2000-11-14 Sugen, Inc. Indolinone combinatorial libraries and related products and methods for the treatment of disease
KR100264807B1 (en) * 1996-01-17 2000-09-01 고바야시 유키오 Intimal hypertrophy inhibitors
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GB9611797D0 (en) * 1996-06-06 1996-08-07 Pharmacia Spa Substituted quinolylmethylen-oxindole analogues as tyrosine kinase inhibitors
GB9613021D0 (en) * 1996-06-21 1996-08-28 Pharmacia Spa Bicyclic 4-aralkylaminopyrimidine derivatives as tyrosine kinase inhibitors
ES2251741T3 (en) * 1996-08-23 2006-05-01 Sugen, Inc. INDOLINONA COMBINATORY LIBRARIES AND RELATED PRODUCTS AND METHODS FOR THE TREATMENT OF DISEASES.
US5917028A (en) * 1996-10-29 1999-06-29 Incyte Pharmaceuticals, Inc. Human phosphoprotein
AU7622698A (en) * 1996-12-05 1998-06-29 Sugen, Inc. Use of indolinone compounds as modulators of protein kinases
US6051593A (en) * 1997-06-20 2000-04-18 Sugen, Inc. 3-(cycloalkanoheteroarylidenyl)-2- indolinone protein tyrosine kinase inhibitors
GB9718913D0 (en) 1997-09-05 1997-11-12 Glaxo Group Ltd Substituted oxindole derivatives
US6133305A (en) 1997-09-26 2000-10-17 Sugen, Inc. 3-(substituted)-2-indolinones compounds and use thereof as inhibitors of protein kinase activity
US6531502B1 (en) 1998-01-21 2003-03-11 Sugen, Inc. 3-Methylidenyl-2-indolinone modulators of protein kinase
AU760046B2 (en) 1998-02-27 2003-05-08 United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The Disubstituted lavendustin a analogs and pharmaceutical compositions comprising the analogs
US6043254A (en) * 1998-04-03 2000-03-28 Boehringer Ingelheim Pharma Kg Indolinones having kinase-inhibiting activity
DE19815020A1 (en) * 1998-04-03 1999-10-07 Boehringer Ingelheim Pharma New substituted indolinones, their production and their use as medicines
US6569868B2 (en) 1998-04-16 2003-05-27 Sugen, Inc. 2-indolinone derivatives as modulators of protein kinase activity
EP1117397A1 (en) * 1998-08-31 2001-07-25 Sugen, Inc. Geometrically restricted 2-indolinone derivatives as modulators of protein kinase activity
KR20010101266A (en) 1998-12-17 2001-11-14 프리돌린 클라우스너, 롤란드 비. 보레르 4-aryloxindoles as inhibitors of jnk protein kinases
US6153634A (en) * 1998-12-17 2000-11-28 Hoffmann-La Roche Inc. 4,5-azolo-oxindoles
AU767138B2 (en) 1998-12-17 2003-10-30 F. Hoffmann-La Roche Ag 4,5-pyrazinoxindoles as protein kinase inhibitors
ATE234830T1 (en) 1998-12-17 2003-04-15 Hoffmann La Roche 4-ALKENYL (AND ALKINYL)OXOINDOLES AS INHIBITORS OF CYCLIN-DEPENDENT KINASES, PARTICULARLY CDK2
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US6492398B1 (en) 1999-03-04 2002-12-10 Smithkline Beechman Corporation Thiazoloindolinone compounds
US6624171B1 (en) 1999-03-04 2003-09-23 Smithkline Beecham Corporation Substituted aza-oxindole derivatives
US6689806B1 (en) 1999-03-24 2004-02-10 Sugen, Inc. Indolinone compounds as kinase inhibitors
EP1165513A1 (en) * 1999-03-24 2002-01-02 Sugen, Inc. Indolinone compounds as kinase inhibitors
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JP2003535038A (en) * 1999-12-30 2003-11-25 スージェン・インコーポレーテッド 3-Heteroarylidenyl-2-indolinone compounds for modulating protein kinase activity and for use in cancer chemotherapy
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PE20030062A1 (en) 2001-05-30 2003-02-08 Sugen Inc ARALKYLSULFONIL-3- (PYRROL-2-ILMETILIDEN) -2-INDOLINONE DERIVATIVES AS KINASE INHIBITORS
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NZ561215A (en) 2005-02-22 2010-12-24 Univ Michigan Small molecule inhibitors of MDM2 and uses thereof
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CN102115469A (en) * 2011-03-21 2011-07-06 浙江大学 Preparation method for indoline-2-one derivative and application of same
US9296730B2 (en) 2012-10-26 2016-03-29 Regents Of The University Of Minnesota Aurora kinase inhibitors
US10487054B2 (en) 2017-04-21 2019-11-26 Regents Of The University Of Minnesota Therapeutic compounds

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Also Published As

Publication number Publication date
FI950859A (en) 1995-02-24
PT658159E (en) 2001-01-31
ATE195734T1 (en) 2000-09-15
JPH08500847A (en) 1996-01-30
AU6971994A (en) 1995-01-24
GR3034854T3 (en) 2001-02-28
EP0658159A1 (en) 1995-06-21
AU679754B2 (en) 1997-07-10
EP0658159B1 (en) 2000-08-23
HU9500954D0 (en) 1995-05-29
ATE360013T1 (en) 2007-05-15
DE69425637T2 (en) 2001-05-03
MX9404885A (en) 1995-01-31
DE69425637D1 (en) 2000-09-28
WO1995001349A1 (en) 1995-01-12
US5656654A (en) 1997-08-12
CA2142472A1 (en) 1995-01-12
EP0987263B1 (en) 2007-04-18
ES2152317T3 (en) 2001-02-01
DE69434955D1 (en) 2007-05-31
PL307741A1 (en) 1995-06-12
EP0987263A2 (en) 2000-03-22
GB9313638D0 (en) 1993-08-18
JP3737826B2 (en) 2006-01-25
ES2300132T3 (en) 2008-06-01
IL110131A0 (en) 1994-10-07
CN1111454A (en) 1995-11-08
NZ267423A (en) 1996-03-26
FI950859A0 (en) 1995-02-24
ZA944730B (en) 1995-07-13
KR950702979A (en) 1995-08-23
EP0987263A3 (en) 2003-10-15
HUT72047A (en) 1996-03-28
DE69434955T2 (en) 2008-01-17
RU95108244A (en) 1997-03-20

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